Abstract
The neuronal and synaptic organisation of the cerebral cortex
appears exceedingly complex, and the definition of a basic
cortical circuit in terms of defined classes of cells and
connections is necessary to facilitate progress of its analysis.
During the last two decades quantitative studies of the synaptic
connectivity of identified cortical neurones and their molecular
dissection revealed a number of general rules that applies to all
areas of cortex. In this review, first the precise location of
postsynaptic GABA and glutamate receptors is examined at cortical
synapses, in order to define the site of synaptic interactions.
It is argued that, due to the exclusion of G protein-coupled
receptors from the postsynaptic density, the presence of
extrasynaptic receptors and the molecular compartmentalisation of
the postsynaptic membrane, the synapse should include
membrane areas beyond the membrane specialisation. Subsequently,
the following organisational principles are examined:

1. The cerebral cortex consists of: (i) a large population of
principal neurones reciprocally connected to the thalamus and to
each other via axon collaterals releasing excitatory amino acids,
and, (ii) a small population of mainly local circuit GABAergic
neurones.

2. Differential reciprocal connections are also formed amongst
GABAergic neurones.

3. All extrinsic and intracortical glutamatergic pathways
terminate on both the principal and the GABAergic neurones,
differentially weighted according to the pathway.

4. Synapses of multiple sets of glutamatergic and GABAergic
afferents subdivide the surface of cortical neurones and are
often co-aligned on the dendritic domain.

5. A unique feature of the cortex is the GABAergic axo-axonic
cell, influencing principal cells through GABAA
receptors at synapses located exclusively on the axon initial
segment.

The analysis of these salient features of connectivity has
revealed a remarkably selective array of connections, yet a
highly adaptable design of the basic circuit emerges when
comparisons are made between cortical areas or layers. The basic
circuit is most obvious in the hippocampus where a relatively
homogeneous set of spatially aligned principal cells allows an
easy visualization of the organisational rules. Those principles
with have been examined in the isocortex proved to be identical
or very similar. In the isocortex, the basic circuit, scaled to
specific requirements, is repeated in each layer. As multiple
sets of output neurones evolved, requiring subtly different needs
for their inputs, the basic circuit may be superimposed several
times in the same layer. Tangential intralaminar connections in
both the hippocampus and isocortex also connect output neurones
with similar properties, as best seen in the patchy connections
in the isocortex. The additional radial superposition of several
laminae of distinct sets of output neurones, each representing
and supported by its basic circuit, requires a co-ordination of
their activity that is mediated by highly selective interlaminar
connections, involving both the GABAergic and the excitatory
amino acid releasing neurones. The remarkable specificity in the
geometry of cells and the selectivity in placement of
neurotransmitter receptors and synapses on their surface,
strongly suggest a predominant role for time in the coding of
information, but this does not exclude an important role also for
the rate of action potential discharge in cortical representation
of information.